Various researches have heretofore made for penem or carbapenem compounds, since they have wide and strong antimicrobial activities. In the production thereof, (1'R, 3R, 4R)-3-(1'-protected hydroxyethyl)-4-acyloxy-2-azetidinone derivatives (i.e., "acyloxyazetidinone derivatives" hereinbelow) are used as an excellent synthetic intermediate and various synthetic methods are reported (see N. Ueyama et al., JP-A-62-84057).
At present, as a production method of acyloxyazetidinone derivatives, the following method is known (see JP-A-3-127773). ##STR2## wherein OR represents a protected hydroxy group, X represents an alkyl or aryl group, and Y represents an acyl group.
Thus, this method is a method capable of safe and efficiently producing the desired acyloxyazetidinone derivatives (V) by reacting (1'R, 3S, 4R)-3-(1'-protected hydroxyethyl)-4-substituted thio-2-azetidinone derivatives (IV) (i.e., "substituted thioazetidinone derivatives" hereinbelow) with a carboxylic acid in the presence of a copper compound.
As explained above, although acyloxyazetidinone derivatives useful as a synthetic intermediate of penem or carbapenem compounds can be produced in an industrial scale from the substituted thioazetidinone derivatives as a starting material, there are various problems in the known methods for producing the starting substituted thioazetidinone derivatives. ##STR3## wherein Hal represents a halogen atom, R.sup.1 represents an alkyl or aryl group, and OR and Y are the same as defined above.
According to the above-mentioned method (see JP-A-61-207373), an optically active 1,3-butanediol (VI) is used as a starting material and the substituted thioazetidinone derivatives (XI) can be obtained at a high yield from the cyclization reaction, with chlorosulfonyl isocyanate (CSI), of the intermediate trans-vinylsulfide (IX) obtained from the starting material through the steps of the substitution at the 1-position, the protection of the hydroxy group at the 3-position, the halogenation and the dehydrohalogenation. This is an excellent method. However, according to the above method, there are still problems that the starting optically active 1,3-butanediol is expensive and also, since the multi-step synthesis is necessary for producing the trans-vinylsulfide (IX), there are problems in the yield thereof. Furthermore, the cis-isomer (X), which is produced as a by-product during the synthesis of the trans-vinylsulfide (IX) and which is extremely difficult to separate from the trans-isomer, affects the selectivity and yield of the subsequent cyclization reaction.
Furthermore, a method for obtaining an optically active 1-substituted-3-hydroxybutane or optically active 1-substituted-3-hydroxybutene from the optical resolution of the ester derivative of racemic 1-substituted-3-hydroxybutane or racemic 1-substituted-3-hydroxybutene, respectively, with lipase (see JP-A-4-228092 and JP-A-4-228093). This method is an effective method in view of the excellent selectivity, but the maximum yield of the optically active substance is as high as 50%.
As mentioned above, there are various problems to be solved in the conventional production method for obtaining the substituted thioazetidinone derivatives and there are strong need to solve these problems.